Design and synthesis of medium-ring lactam libraries inspired by octalactin a. A convergent-divergent approach.

Abstract

Small molecule compound libraries based on medium rings1 are virtually unknown.2 This critical gap in the literature is probably caused by two main factors. First, medium ring natural products are themselves uncommon and therefore less likely to be the object of total synthesis efforts.3 Second, there is a widely held view that medium rings remain the most challenging and difficult systems to synthesize.4 As part of a program to identify interesting chemotypes for library development, we examined several medium-ring natural products. One system in particular, namely, octalactin A (1) (Figure 1),5 continues to attract intense interest because of its fascinating architecture and potent antitumor profile.6